title: Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma.
abstract: Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: L
authors.initials: L
authors.lastname: Trandafir
authors.forename: P
authors.initials: P
authors.lastname: Ruffié
authors.forename: C
authors.initials: C
authors.lastname: Borel
authors.forename: I
authors.initials: I
authors.lastname: Monnet
authors.forename: P
authors.initials: P
authors.lastname: Soulié
authors.forename: D
authors.initials: D
authors.lastname: Adams
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
authors.forename: J P
authors.initials: JP
authors.lastname: Armand
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008654:Mesothelioma / Q000628:therapy*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D002945:Cisplatin